| 1. |
- Capogna, E., et al.
(author)
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Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers-in cognitively unimpaired older adults
- 2023
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In: Brain, behavior, and immunity. - 0889-1591 .- 1090-2139. ; 113, s. 56-65
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Journal article (peer-reviewed)abstract
- Concentrations of pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-8 (IL-8) - are increased with age and in Alzheimer's disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62-91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time - up to 9 years - with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-& beta; (A & beta;-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/A & beta;-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an upregulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.
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| 2. |
- Fjell, A. M., et al.
(author)
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Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression
- 2020
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In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:4, s. 2144-2156
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Journal article (peer-reviewed)abstract
- Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker beta-amyloid (AD) Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homerla, a neural protein coded by the HOMER1 gene, which has also been implicated in brain A beta accumulation. Here, we tested whether the relationship between cortical A beta accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, A beta correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-A beta relationship followed closely the A beta accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and A beta accumulation may involve Homer1 activity in the cortical regions, where harbor A beta deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.
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| 3. |
- Henjum, K., et al.
(author)
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CSF sTREM2 in deliriumrelation to Alzheimer's disease CSF biomarkers A42, t-tau and p-tau
- 2018
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In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 15
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Journal article (peer-reviewed)abstract
- BackgroundDelirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer's disease.MethodsWe analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n=120), and some of the patients developed delirium (n=65). A medical delirium cohort (n=26) was also examined. ELISA was used to determine the level of sTREM2 in CSF.ResultsDelirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p=0.046, n=15, n=44), particularly among patients developing delirium after CSF sampling (p=0.02, n=7, n=44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (r(S)=0.39, p=0.002, n=60) and correlated well with the CSF Alzheimer's disease biomarkers, A42, and t-tau/p-tau (r(S)=0.40, p=0.002, r(S)=0.46, p<0.001/ r(S)=0.49, p<0.001, n=60). Among patients with dementia, the level of A38 and A40 also correlated positively with sTREM2 in CSF (A38(MSD)r(S)=0.44, p=0.001; A40(MSD)r(S)=0.48, p<0.001; A42(MSD)r(S)=0.43, p<0.001, n=60).ConclusionThe findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.
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| 4. |
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| 5. |
- Leavey, N., et al.
(author)
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Study protocol: ASCRIBED: the impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in dementia: a study in acute hip fracture patients
- 2019
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In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 19:1
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Journal article (peer-reviewed)abstract
- Background Hip fracture represents a substantial acute inflammatory trauma, which may constitute a significant insult to the degenerating brain. Research suggests that an injury of this kind can affect memory and thinking in the future but it is unclear whether, and how, inflammatory trauma injures the brain. The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients (ASCRIBED) explores this relationship, to understand the effect of inflammation on the progression of dementia. Methods This protocol describes a multi-centre sample collection observational study. The study utilises the unique opportunity provided by hip fracture operations undertaken via spinal anaesthesia to collect cerebrospinal fluid (CSF) and blood, to investigate the impact of acute brain inflammation caused by hip fracture on the exacerbation of dementia. We will recruit 200 hip fracture patients with a diagnosis or evidence of dementia; and 200 hip fracture patients without dementia. We will also recruit 'Suitable informants', individuals in regular contact with the patient, to provide further proxy evidence of a patient's potential cognitive decline. We will compare these 400 samples with existing CSF and blood samples from a cohort of dementia patients who had not experienced a systemic inflammatory response due to injury. This will provide a comparison between patients with and without dementia who are suffering a systemic inflammatory response; with stable patients living with dementia. Discussion We will test the hypothesis that hip fracture patients living with dementia show elevated markers of brain inflammation, as well as neuronal injury and Alzheimer-related plaque pathology, in comparison to (1) stable patients living with dementia and (2) hip fracture patients without dementia, as measured by biomarkers in CSF and blood. The findings will address the hypothesis that systemic inflammatory events can exacerbate underlying dementia and inform the search for new treatments targeting inflammation in dementia.
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| 6. |
- Vidal-Pineiro, D., et al.
(author)
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Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults
- 2022
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 116, s. 80-91
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Journal article (peer-reviewed)abstract
- It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-beta (A beta 42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3) = , total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by A beta 42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers. (C) 2022 The Author(s). Published by Elsevier Inc.
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| 7. |
- Aksnes, M., et al.
(author)
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Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals
- 2023
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In: Neurobiology of Aging. - 0197-4580. ; 131, s. 11-23
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Journal article (peer-reviewed)abstract
- Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-& beta;42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging. & COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 8. |
- Hall, R. J., et al.
(author)
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CSF biomarkers in delirium: a systematic review
- 2018
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In: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230. ; 33:11, s. 1479-1500
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Journal article (peer-reviewed)abstract
- ObjectiveMethodsIn recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies. In this systematic review, we screened MEDLINE, EMBASE, PsycINFO, Web of Science, PubMed and the Cochrane Library for articles on CSF biomarkers in delirium, published on 3 September 2016. Studies were required to use Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria for delirium or a validated tool. We excluded case reports. There were no other restrictions on study type. ResultsConclusionsWe identified 3280 articles from our initial search, and 22 articles were included in this review. All studies were prospective, including over 400 patients with delirium and 700 controls. More than 70 different biomarkers were studied. Studies could not be compared with each other for meta-analysis because of their heterogeneity and varied widely in their risk of bias and quality assessments. The 22 studies identified in this review reveal a small but growing literature, in which many of the important hypotheses in delirium pathogenesis have been examined, but from which few firm conclusions can currently be drawn. Nevertheless, the overall interpretation of the literature supports the vulnerable brain concept, that is, that biomarker evidence of, for example, Alzheimer's disease pathology and/or neuroinflammation, is associated with delirium.
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| 9. |
- Henjum, K., et al.
(author)
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Cerebrospinal fluid catecholamines in Alzheimer's disease patients with and without biological disease
- 2022
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Journal article (peer-reviewed)abstract
- Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer's disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOE epsilon 4 status verified the findings. In restricted analyses comparing A+T+ patients to A-T- cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A-T- cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.
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| 10. |
- Hov, K. R., et al.
(author)
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Cerebrospinal Fluid S100B and Alzheimer's Disease Biomarkers in Hip Fracture Patients with Delirium
- 2017
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In: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 7:3, s. 374-385
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Journal article (peer-reviewed)abstract
- Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electro-chemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. Results: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 mu g/L [0.91-1.29]) and patients who never developed delirium (n = 46, 1.08 mu g/L [0.92-1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 mu g/L [1.08-1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (= 60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. Conclusions: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology. (c) 2017 The Author(s) Published by S. Karger AG, Basel.
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| 11. |
- Idland, Ane Victoria, et al.
(author)
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Preclinical amyloid-β and axonal degeneration pathology in delirium
- 2016
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 55:1, s. 371-379
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Journal article (peer-reviewed)abstract
- Background: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. Objective: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. Methods: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ42, T-tau, and P-tau were analyzed. Results: In patients without dementia, we found lower CSF Aβ42 levels (median, 310ng/L versus 489ng/L, p=0.006), higher T-tau levels (median, 505ng/L versus 351ng/L, p=0.02), but no change in P-tau in patients who developed delirium (n=16) compared to those who remained lucid (n=49). Delirious patients also had lower ratios of Aβ42 to T-tau (p<0.001) and P-tau (p=0.001) relative to those without delirium. CSF Aβ42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n=54) and without delirium (n=10). Conclusion: The reduction in CSF Aβ42, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.
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| 12. |
- Krogseth, M., et al.
(author)
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Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population-based cohort
- 2023
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In: Lancet Healthy Longevity. - 2666-7568. ; 4:8
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Journal article (peer-reviewed)abstract
- Background Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL). Methods In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised. Findings Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference -1.5, 95% CI -2.9 to -0.1). We found an interaction between previous MoCA score and delirium (beta -0.254, 95% CI -0.441 to -0.066, p=0.010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (-1.7, 95% CI -2.8 to -0.6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (-1.8, -2.5 to -1.1). Delirium was directly linked with a predicted value of 1.2 pg/mL (95% CI 1.02 to 1.40, p=0.029) increase in NfL. Interpretation In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.
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| 13. |
- Neerland, B. E., et al.
(author)
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Fatty Acid-Binding Protein 3 in Cerebrospinal Fluid of Hip Fracture Patients with Delirium
- 2020
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 77:1, s. 183-190
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Journal article (peer-reviewed)abstract
- Background: Delirium is associated with dementia and thus biomarkers reflecting neurodegeneration are of interest. Fatty acid-binding protein 3 (FABP3) is a cytoplasmic neuronal protein that has been isolated from the brain. It is released following brain injury and concentrations in cerebrospinal fluid (CSF) are also higher in neurodegenerative disorders such as Alzheimer's disease (AD). Objective: To examine the relationship between CSF FABP3 concentration and delirium in hip fracture patients compared to a group of cognitively normal controls. Methods: CFS FABP3 concentration was measured in 128 hip fracture patients with (n = 71) and without (n = 57) delirium, and in cognitively unimpaired adults >= 64 years (n = 124) undergoing elective surgery. Results: CSF FABP3 (pg/ml) concentration (median (IQR)) was higher in hip-fracture patients compared to cognitively normal controls (5.7 (4.2-7.7) versus 4.5 (3.4-6.1), p < 0.001). There was a significant weak correlation between age and CSF FABP3 (rho = 0.3, p < 0.001). After adjustment for age, the association between CSF FABP3 and hip-fracture was no longer statistically significant (13 = 0.05, p = 0.5). There were no significant differences in CSF FABP3 concentration between hip fracture patients with (5.4 (4.1-8.2)) and without (5.8 (4.2-7.2)) delirium. CSF FABP3 concentration correlated positively with CSF AD biomarkers p-tau (rho = 0.7, p <0.01) and t-tau (rho = 0.7, p < 0.01). Conclusion: CSF FABP3 concentrations were higher in hip fracture patients compared with cognitively normal older adults, indicating ongoing age-related neurodegeneration in these patients. There were no differences of CSF FABP3 concentrations across delirium groups, suggesting that neuronal damage or degeneration reflected by FABP3 may not be directly linked to delirium pathophysiology.
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| 14. |
- Page, V. J., et al.
(author)
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Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients
- 2022
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 80
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Journal article (peer-reviewed)abstract
- Background Delirium predicts poor outcomes, however identifying patients with the worst outcomes is challenging. Plasma neurofilament light protein (NfL) is a sensitive indicator of neuronal damage. We undertook an exploratory observational study to determine the association between plasma NfL and delirium in the critically ill.& nbsp;Methods MoDUS was a randomised placebo-controlled delirium trial of simvastatin done in an UK adult general ICU. We measured NfL levels in plasma samples using a Single molecule array (Simoa) platform. We explored associations between patient's plasma NfL levels and number of delirium days, and clinical outcomes. The control group for baseline NfL were preoperative patients undergoing major surgery.& nbsp;Findings The majority of critically ill patients already had a high NfL level on admission. Patients with higher plasma NfL levels at days one and three spent more days in delirium or deep sedation. Patients with zero or one day in delirium or deep sedation had day one mean concentrations of 37.8 pg/ml (SD 32.6) compared with 96.5 pg/ml (SD 106.1)) for patients with two days or more, p-value 0.002 linear mixed effects model.& nbsp;Survivors discharged before 14 days had lower mean plasma NfL concentrations compared to those with longer hospital stays and/or who died within six months. The area under ROC curve for predicting death within six months using day one NfL was 0.81 (0.7,0.9).& nbsp;Interpretation Measurement of plasma NfL within three days of admission may be useful to identify those patients with worse clinical outcomes, and as an enrichment strategy for future delirium interventional trials in the critically ill.& nbsp;Copyright (C)& nbsp;2022 The Author(s). Published by Elsevier B.V.& nbsp;
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| 15. |
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